Prostate function support formula

ABSTRACT

The invention provides unit dosage forms and methods that are effective to improve prostate function. Such unit dosage forms and methods are useful to decrease bladder discomfort and improve urinary flow in men.

RELATED APPLICATIONS

This is a continuation application of U.S. patent application Ser. No.16/867,386, filed May 5, 2020; which is a divisional application thatclaims priority to U.S. patent application Ser. No. 15/829,797 filed onDec. 1, 2017; the contents of the foregoing of which are hereinincorporated by reference in its entirety.

BACKGROUND OF THE INVENTION

The prostate is a gland that is part of the male reproductive systemsurrounding the urethra at the neck of the bladder. The main function ofthe prostate is to make a thin fluid (semen) that lubricates the urethraand transports sperm. As men age, the prostate loses its originalstructure and function which may lead to urinary problems. Commonprostate conditions include prostate cancer which ranks second mostcommon cancer in men. One in seven men will be diagnosed with prostatecancer during his lifetime and is the third leading cause of cancerdeath in men in the USA (American Cancer Soc. 2017). Symptoms ofprostate cancer include difficulty urinating, blood in semen, pelvic andbone pain and erectile dysfunction. Treatment includes radiationtherapy, hormone therapy, surgery, chemotherapy, and cryosurgery.

Benign Prostatic Hypertrophy (BPH)—Enlarged Prostate is another commonprostate condition in men, with a prevalence of 50%-60% amongst men 60years or older and 90% for men 70 years or older (Roehrborn, C. G.“Benign Prostatic Hyperplasia: An Overview”, Reviews in Urology 7,Suppl. 9 (2005) S3-S14). Approximately 14 million men in the UnitedStates have symptoms of BPH. Men with symptomatic BPH have a 23%lifetime risk of developing acute urinary retention (AUR) if leftuntreated (Rosenberg, M. T., et al, “STEP. Simplified Treatment of theEnlarged Prostate”, Int. J. Clin. Pract. (2010), 64(4):488-496).Symptoms of BPH include urinary frequency, nocturia, difficultyurinating, and dribbling. Treatment includes alpha blockers, 5-alphareductase inhibitors, tadalifil, and surgery.

Yet another prostate condition is Prostatitis; the most common urinarytract problem for men younger than age 50 and the third most commonurinary tract problem for men older than age 50. Symptoms of prostatitisinclude painful or difficult urination and pain in the groin, pelvicarea or genitals. Treatment includes antibiotics, alpha blockers, andanti-inflammatory agents.

A need exists for safe and effective supplements to treat prostateconditions.

SUMMARY OF THE INVENTION

Applicant has determined that the beneficial effects of the presentinvention, a Prostate Function Support Formula are surprising andunexpected to support and enhance prostate function.

The present invention is a dietary supplement to provide prostatefunction support by safely and effectively supporting prostate health,reduce bladder discomfort and improve urinary flow. The presentinvention is comprised of clinically tested ingredients, includingvitamins, minerals, herbs and a proprietary blend of naturalingredients. Drug side effects are not expected since the presentinvention does not include non-drug ingredients.

In one embodiment the invention provides a unit dosage form suitable fororal administration in a human comprising:

about 300 mg of Saw Palmetto;

about 450 mg of Beta-Sitosterol;

about 150 mg of Pygeum Africanum;

about 75 mg of Green Tea extract;

about 15 mg of Lycopene; and

about 30 mg of Stinging Nettle.

In one embodiment, the unit dosage form further comprises Vitamin E.

In one embodiment, the unit dosage form further comprises Vitamin B-6

In one embodiment, the unit dosage form further comprises zinc as zincgluconate.

In one embodiment, the unit dosage form further comprises selenium asamino acid chelate.

In one embodiment, the unit dosage form further comprises copper ascopper gluconate.

In one embodiment, the unit dosage form further comprises Quercetin(2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one).

In one embodiment, the unit dosage form further comprises one or moreamino acids selected from L-alanine, L-glutamic acid and glycine.

In one embodiment, the unit dosage form further comprises one or moreexcipients selected from hydroxypropyl methylcellulose, riceconcentrate, and silica.

In one embodiment, the unit dosage form further comprises one or moreexcipients selected from gelatin, magnesium stearate, stearic acid, andmicrocrystalline cellulose.

In one embodiment, the unit dosage form is formulated as a capsule.

The invention includes a method to improve prostate function in a man inneed thereof comprising administering the unit dosage form of thepresent invention.

Applicant has determined that men taking the unit dosage form of thepresent invention report improvements in prostate function, includingdecreased bladder discomfort and improved urinary flow.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows ingredients of the present invention: Saw Palmetto, BetaSitosterol, Quercetin, Stinging Nettle, Pygeum Africanum, and Green Tea;

FIG. 2 shows ingredients of the present invention: Lycopene, Zinc,Vitamins B6 and E, Amino Acids, Selenium, and Copper;

FIG. 3 shows a product label for a composition of the invention; and

FIG. 4 shows supplement facts of the present invention.

DETAILED DESCRIPTION

As used herein, the term “about” has its generally accepted meaning. Inone embodiment, the term about means±10% of the associated value. Forexample, about 100 mg means 100 mg±10 mg. In one embodiment, the termabout means±5% of the associated value. For example, about 100 mg means100 mg±5 mg. In one embodiment, the term about means±2% of theassociated value. For example, about 100 mg means 100 mg±2 mg. In oneembodiment, the term about means±1% of the associated value. Forexample, about 100 mg means 100 mg±1 mg.

The present invention is a dietary supplement formulated to supporthealthy prostate function, reduce bladder discomfort, and promoteurinary tract health.

Without limiting to any particular mechanism-of-action, the individualingredients of the present invention have demonstrated anti-oxidant,anti-inflammatory, chemopreventative, and immunomodulatory properties inin vitro, in vivo, and/or clinical studies. Both individual andcombination of the ingredients have bee n clinically studied inprospective, open label, randomized, interventional or observationalstudies.

The recommended dosage for the present invention is 3 tablets per daydosing regimen by oral administration in men.

In one embodiment, a unit dosage form of the invention may contain oneor more pharmaceutical diluents or excipients. For example, in oneembodiment a unit dosage form of the invention may comprisemicrocrystalline cellulose, silicon dioxide, and magnesium stearate. Inanother embodiment a unit dosage form of the invention comprises one ormore excipients selected from hydroxypropyl methylcellulose, riceconcentrate, and silica. In another embodiment a unit dosage form of theinvention comprises one or more excipients selected from gelatin,magnesium stearate, stearic acid, and microcrystalline cellulose.

The present invention contains Saw Palmetto, a Tier 2 supplementcontaining fatty acids and beta-sitosterols, commonly used to help menwith prostate or urinary symptoms. Saw Palmetto has been shown in vivo(rat) to reduce the weight and inhibit growth of prostate (Talpur, N. etal “Comparison of Saw Palmetto, extract and whole berry, and cernitin onprostate growth in rats”, Mol. Cell. Biochem. (2003) 250(1-2):21-26).Saw Palmetto is clinically shown to be comparable or more effective thanpharmaceutical drugs for pain and urinary symptoms associated withprostatitis and BPH (Cai, T. et al, Int. J. Antimicrob. Agents (2009)33(6):549-553; Pais, P. et al, Adv. Ther. (2010) 27(8):555-563;Bondarenko, B. et al, (2003) Phytomedicine). Saw Palmetto may helpreduce the pressure that the prostate exerts on the urethra by shrinkingthe lining of the prostate. Saw Palmetto may reduce cancer cellproliferation and inflammation (Goldmann, W. H. et al, Cell Biol. Int(2001) 25(11):1117-1122; Yang, Y. et al, Intl. Jour. Onc. (2007)31(3):593-600). Additional clinical studies on Saw Palmettol have showna statistically significant improvement in urinary symptoms in men withLUTS (Lower urinary tract symptoms), a group of clinical symptomsinvolving the bladder, urinary sphincter, urethra, and, prostate(Gerber, G. S. et al, Urology (2001) 58960-4, 964-965); progress in CPSI(Chronic Prostitis Symptom Index) scores (Kraychick, S. G. et al,27^(th) Annual Euro. Assoc. of Urology Cong. Feb. 24-28, 2012, ParisFR), and others (Carraro, J. C. et al, Prostate (1996) 28(4):231-240;Sinescu, I. et al, Urol. Intl. (2011) 86:284-289).

Beta-sitosterols have been shown clinically to decrease levels of DHT(hormone linked to BPH) and significantly improve urinary flow (Berges,R. R. et al, (Lancet (1995) 345:1529-1532; Klipper, K. F. et al, BR J.Urol. (1997) 80(3):427-432). Data comparing men treated withbeta-sitosterol to those receiving placebo indicate a significantdecrease in symptom scores in the beta-sitosterol group after three andsix months of treatment. In a follow-up study, these improvements weremaintained for an additional 18 months of observation.

Stinging Nettle is an herb commonly used to treat urinary problemsassociated with BPH and urinary tract infections (UTI). Stinging Nettleis clinically shown to relieve difficulty in urinating and urge tourinate caused by BPH (Ghorbanibirgani, A. et al, Iran. Red Cres. Med.J. (2013) 15(1):9-10; Pavone, C. D. et al, Yrologia (2010) 77(1):43-51;Safarinejad, M. R. et al, J. Her. Pharmacother. (2005) 5(4):1-11). Invitro, Stinging Nettle is seen to interfere with SHGB and prevent itfrom combining with androgens (Nahata, A. et al, Andrologia (2012)44:396-409). Stinging Nettle acts a 5-α-reductase inhibitor, preventingthe conversion of testosterone to Dihydrotestosterone (DHT) (Lopatkin,N. et al, World J. Urol. 2005). The German Commission E approves the useof nettle leaf as supportive therapy in patients with LUTS (combinedwith immune and antimicrobial therapy) and to prevent and treatformation of urinary gravel. Stinging Nettle leads to significantreduction in IPSS (International Prostate Symptoms Score), serum PSA(prostate specific antigen) and prostate size in a prospective,randomized double blind, placebo controlled cross over clinical trial of558 men with BPH (Safarinejad, M. R. et al, J. Her. Pharmacother. (2005)5(4):1-11). In a similar trial of 100 men with BPH, the treatment grouphad better effects in relieving clinical symptoms in BPH patientscompared to placebo (Ghorbanibirgani, A. et al, Iran. Red Cres. Med. J.(2013) 15(1):9-10). In one embodiment the Stinging Nettle is used as aherb powder.

Combination therapy clinical studies of Saw Palmetto with StingingNettle or Quercetin reduced the symptoms in 85% of LUTS secondary to BPHpatients (Pavone, C. D. et al, Yrologia (2010) 77(1):43-51), showed IPSSimprovement (Bondarenko, B. et al, (2003) Phytomedicine), was superiorto placebo (Lopatkin, N. et al, World J. Urol. 2005), and relievedsymptoms of prostatitis (Cai, T. et al, Intl. J. Antimicrob. Agents(2009) 33(6):549-553).

Quercetin (CAS Reg. No. 117-39-5), named as2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one, is a plantpolyphenol from the flavonoid group, found in many fruits, vegetables,leaves, and grains. Quercetin is a Tier 1 supplement and naturallyoccurring flavonoid recognized as a potent antioxidant,anti-inflammatory and gives relief of symptoms associated withprostatitis. Quercetin promoted prostate cancer cells apoptosis andcaspase activation in vitro (Kim, Y. H. et al, J. Cell. Biochem. (2007)100(4):998-1009; Lee, D. H. et al, Biochem. Pharmacol. (2008)75(12):2345-2355; Xing, N. et al, Carcinogenesis (2001) 22:409-414;Wang, G. et al, Oncol. Rep. (2013) 30:357-363). Quercetin is effectivein vivo in combination with finasteride to reduce prostate weight andanti-tumor activity (Ma, Z. et al, J. Endocrinol. (2004) 181(3):493-507;Ferry, D. R. et al, Clin. Cancer Res. (1996) 2(4):659-668). Quercetin isclinically shown to provide symptomatic improvement in CP/CPPS and shownto enhance the efficacy of antibiotic to treat CP when used incombination with other natural ingredients; saw palmetto and stingingnettle (Cai, T. et al, Intl. J. Antimicrob. Agents (2009)33(6):549-553). Quercetin is a recommended treatment through the UPOINTSystem for Prostatitis Treatment used by medical professionals (Shoskes,D. A. et al, Urology (2010) 75(6); Shoskes, D. A. et al, Urology (1999)54(6):960-963) demonstrating decrease in IPSS in a randomized,double-blind, placebo controlled clinical trial. Quercetin has an effecton human prostate tumor in vivo xenografts in mice and inhibits prostatecancer cell proliferation in vitro (Yang, F. et al, Oncology Reports(2016) 35(3):1602-1610).

Pygeum Africanum is a Tier 2 herb used to promote prostate and bladderhealth, BPH, and nocturia (also known as nycturia, the need to urinateat night) reduction. The major active components of Pygeum Africanum arefat-soluble sterols (phytosterols) and fatty acids that can inhibit theproduction of DHT (dihydrotestosterone), pro-inflammatory prostaglandinsin the prostate (Andro, M. C. et al, Curr. Ther. Res. (1995) 56:796-817;Monograph. “Pygeum africanum”, Alternative Medicine Review. (2002)V7(1)), and triterpenes and ferulic acid nesters to block theaccumulation of cholesterol in the prostate. Pygeum Africanum is shownin vitro and in vivo to modulate bladder contractility, inhibit cancercell proliferation and viability, promote cell apoptosis, and suppressproduction of prostaglandins (Levin, R. M. et al, J. Urol. (1996)156:2084-2088; Santa Maria, M. A., et al, Arch. Esp. Urol. (2003)56(4):369-378; Boulbes, D. et al, BJU Int. (2006) 98(5):1106-1113;Quiles, M. T. et al, Prostate (2010) 70(10):1044-1053; Papaioannou, M.et al, Invest. New Drugs (2010) 28(6):729-743). Pygeum Africanum isclinically shown to improve urinary flow, reduce nocturia, and improveprostate symptoms, urinary parameters, and sexual function in men withBPH or prostatitis (Andro, M. C. et al, Curr. Ther. Res. (1995)56:796-817; Carani, C. et al, Arch. Ital. Urol. Nefrol. Androl. (1991)63(3)341-345; Chatelain, C. et al, Urology (1999) 54(3):473-478; Barlet,A. et al, Wein Klin. Wochesschr. (1990) 102:667-673; Breza, J. et al,Curr. Med. Res. Opin. (1998) 14(3):127-139).

Green Tea Extract is a Tier 2 supplement with antioxidant qualities toprovide support for prostate health, normal prostate size, andanti-cancer protective effect. Green Tea Extract is shown to regulateDHT production and hormones that influence prostate volume. Catechins(polyphenol compounds) in green tea shown to have anti-inflammatoryqualities, reduce infection, enhance the immune system, and regulate theproduction and activities of hormones (Alschuler, L. et al, Am. J.Natur. Med. (1996) 5:28-31; Graham, H. N. et al, Prev. Med. (1992)21:334-350). In vitro, in vivo and clinical studies identified EGCG(green tea catechin) to be a modulator of molecular pathways to prostatecarcinogenesis (Nihal, A. et al, Nutr. Rev. (1999) 57:78-83; Ahmad, N.et al J. Natl. Cancer Inst. (1997) 89:1881-1886). In vitro EGCG acts asan anti-androgen antagonist, suppresses prostate cancer cellproliferation and production of prostate-specific antigen (PSA), reducestumor size and delays development of prostate tumors in TRAMP mice(Adhami, V. M. et al, Clin. Cancer Res. (2009) 15(6):1947-1953; Gupta,S. et al, Proc. Natl. Acad. Sci. USA (2001) 98(18):10350-10355; Kim. S.J. et al, Cancer Prev. Res. (2014) 7(4):435-444). Clinically shown inrandomized trials to reduce overall rate of progression of prostatecancer in men with HGPIN (high-grade prostatic intraepithelialneoplasia), an abnormality of prostatic glands and believed to precedethe development of prostate adenocarcinoma, the most common form ofprostate cancer (Kumar, N. B. et al, Cancer Prev. Res. (Phila) (2015)8(10):879-887; Bettuzzi, S. et al, Cancer Res. (2006) 66(2):1234-1240;Brausi, M. et al, Eur. Urol. (2008) 54(2):472-473). Other clinicaltrials with great tea and/or its components shown benefits of decreasedPSA levels, and other biomarkers correlated with prostate cancer(Henning, S. M. et al, Prostate (2015) 75(5):550-559; McLarty, J. et al,Cancer Prev. Res. (2009) June 19; Nguyen, M. et al, Cancer Prev. Res.(Phila) (2012) 5(2):290-298).

Lycopene is a Carotenoid produced by plants. Lycopene enhancesantioxidant response to support prostate health and is generallyrecognized as safe (GRAS). Epidemiological/Clinical studies linkincreased lycopene consumption with decreased prostate cancer risk,decreasing serum PSA levels, suppression of tumor growth and supportingurinary function (Obermuller-Jevic, U. C. et al, J. Nutr.133(11):3356-3360; Ford, N. A. et al, Nutr. Cancer (2011) 63(2):256-263;Yang, C. M. et al, J. Nutr. Biochem. (2012) 23(1):8-17; Zhang, X. et al,Chin. Med. J. (2010) 123(16):2231-2236; Mariani, S. et al, Int. J. Mol.Sci. (2014) 15(1):143301440; Qiu, X. et al, Cancer Prev. Res. (Phila)(20-13) 6(5):419-427; Tang, Y. et al, Neoplasia (2011) 13(2):108-119;Gann, P. H. et al, Cancer Res. (1999) 59(6):1225-1230). Animal studiesshow antitumorigenic effect (Yang, C. M. et al, Mol. Nutr. Food Res.(2011) 55(4):606-612; Yang, C. M. et al, J. Nutr. Biochem. (2012)23(9):1155-1162). Lycopene is shown in vitro and in vivo to enhance theantioxidant response of prostate cells, inhibit proliferation,demonstrate chemopreventive effect induce apoptosis and decrease themetastatic capacity of prostate cancer cells and may affect insulin-likegrowth factor (IGF) intracellular pathway in prostate cancer cells(Konijeti, R. et al, Prostate (2010) 70(14):1547-1554; Kim, H J. S. etal, Nutr. Cancer (2003) 47(1):40-47). Clinical trials with lycopeneshowed reduction of PSA levels (Kucuk, O. et al, Exp. Biol. Med. (2202)227(10):881-885; Schwarz, S. 1391(1):49-53; Mohanty, N. K. et al, Urol.Oncol. (2005) 23(6):383-385; Ansari, M. S. et al, BJU Intl. (2003)92(4):375-378).

Vitamin E, an essential vitamin, and Selenium, an essential mineral,have antioxidative properties and are widely used to prevent damage tothe cells, tumor suppression in prostate cancer and provide immunesupport. Vitamin E and selenium have been shown in vitro and in vivo toreduce risk of prostate cancer, suppress tumor progression and cellapoptosis (Pinto, J. T. et al, Int. J. Cancer (2007) 120(7):1410-1417;Zhang, Y. et al, Proc. Natl. Acad. Sci. USA (2002) 99(11):7408-7413;Limpens, J. et al, J. Nutr. (2006) 136:1287-1293; Malafa, M. et al,Intl. J. of Cancer (2006) 118(10):2441-2447). Selenium has shown invitro to decrease the activity of the androgen receptor leading toapoptosis and growth inhibition on prostate cancer cells, increaselevels of p53 (tumor suppression) and regulate oxidative and the immunesystem (Kong et al, Biomaterials (2011) 32(27):6515-6522; Sarveswaran,S. et al, Int. J. Oncol. (2010) 36(6):1419-1428). Higher blood seleniumconcentrations have been clinically associated with decreased prostatecancer (EPIC and Physicians' health study) and decrease PSA levels(Clark, L. C. et al, British J. of Urol. 1998) 81:730-734; Allen, N. E.et al, Am. J. Clin. Nutr. (2008) 88(6):1567-1575; Li, H. et al, J. Natl.Cancer Inst. (2004) 96(9):696-703; Meyer, H. A. et al, Cancer Epidemiol.Bioimarkers Prev. (2009) 18(9):2386-2390).

Vitamin B-6 is required for proper prostate function cell repair andimmune health, and the proper manufacture and metabolism of hormonesnecessary for prostate health.

Zinc is a Tier 3 supplement for prostatitis, prostate cancer and BPH.Zinc induces apoptosis and antiproliferative effects on prostate cancerand BPH cells in vitro (Costello, L. C. et al, Open Urol. Nephrol. J.(2008) 1; Franklin, R. B. et al, Arch. Biochem. Biophys. (2007)463(2):211-217. Zinc plays a role in testosterone, sperm formation andmotility, and DNA damage repair (Netter, A. et al, Arch. Androl. (1981)7(1):69-73). Clinical experience associates an inverse relationshipbetween zinc intake and risk of prostate issues (Medarova, Z. et al, Am.J. Cancer Res. (2014) 4(4):385-393; Costello, L. C. et al, Mol. Cancer.(2006) 5:17; Mahmoud, A. M. et al, PLoS ONE (2016) 11.11 e0165956 PMC).

“Zinc gluconate” is the zinc salt of gluconic acid. It is an ioniccompound consisting of two anions of gluconate for each zinc (II)cation. Zinc gluconate is available from a number of commercial sources.

“Selenium as an amino acid chelate” is an enhanced form of selenium, avital trace element nutrient with multiple roles in the growth andfunctioning of living cells in higher animals and humans. Inorganic saltforms of selenium such as sodium selenite and sodium selenite whencomplexed or incorporated with amino acids, such as aspartic acid andmethionine, form selenium-amino acid chelates with enhanced absorptionproperties.

“Copper gluconate” is the copper salt of gluconic acid. It is soluble inwater and insoluble in ethanol. Copper gluconate is available from anumber of commercial sources.

All publications, patents, and patent documents are incorporated byreference herein, as though individually incorporated by reference. Theinvention has been described with reference to various specific andpreferred embodiments and techniques. However, it should be understoodthat many variations and modifications may be made while remainingwithin the spirit and scope of the invention.

1-8. (canceled)
 9. A method to improve prostate function, comprisingadministering a composition comprising: saw palmetto; beta-sitosterol;and stinging nettle, wherein the composition is provided in a capsuledosage form.
 10. The method of claim 9, wherein the compositioncomprises about 300 mg saw palmetto.
 11. The method of claim 10, whereinthe saw palmetto is a 40-45% extract.
 12. The method of claim 11,wherein the composition further comprises gelatin, magnesium stearateand/or silicon dioxide.
 13. The method of claim 12, wherein thecomposition further comprises gelatin, magnesium stearate, and silicondioxide.
 14. The method of claim 13, wherein the composition furthercomprises pumpkin seed powder.
 15. The method of claim 9, wherein thecapsule is administered orally.
 16. The method of claim 9, wherein themethod also decreases bladder discomfort and/or improves urinary flow.17. A method to decrease bladder discomfort, comprising orallyadministering a composition comprising: saw palmetto; beta-sitosterol;stinging nettle; gelatin; magnesium stearate; and silicon dioxide,wherein the composition is provided in a capsule dosage form.
 18. Themethod of claim 17, wherein the composition comprises about 300 mg sawpalmetto.
 19. The method of claim 18, wherein the saw palmetto is a40-45% extract.
 20. The method of claim 19, wherein the compositionfurther comprises pumpkin seed powder.
 21. The method of claim 17,wherein the method also improves urinary flow.
 22. A method to improveurinary flow, comprising orally administering a composition comprising:saw palmetto; beta-sitosterol; stinging nettle; gelatin; magnesiumstearate; and silicon dioxide, and wherein the composition is providedin a capsule dosage form.
 23. The method of claim 22, wherein thecomposition comprises about 300 mg saw palmetto.
 24. The method of claim23, wherein the saw palmetto is a 40-45% extract.
 25. The method ofclaim 24, wherein the composition further comprises pumpkin seed powder.26. The method of claim 22, wherein the method also decreases bladderdiscomfort.